Diarrhea (travelers diarrhea or TD) is a major health problem when traveling to
developing countries. When visiting high-risk areas in Latin America, Africa, the
Middle East, and Asia, diarrhea rates of between 20% to 50% have been reported. The
syndrome of TD is caused by infection acquired through ingestion of fecally contaminated
food or beverages. Escherichia coli, a common species of enteric bacteria, is the leading
pathogen, although a host of other bacteria, viruses, and protozoa have also been
implicated. Usually self-limited, traveler's diarrhea is more of an inconvenience than a
life-threatening process.

Risk factors for development of travelers' diarrhea include adventurous behavior,
consumption of unclean water or food, and special hosts such as those that are immune
suppressed or are taking H2 blockers. Prevention is the mainstay of therapy in this
illness and patient education is the first step. Unfortunately education about risk
factors fails to modify risky behavior. This includes avoiding untreated tap water, ice
cubes, unpasteurized milk products, salads, food from street vendors, and dining in
unhygienic-appearing restaurants. Well-cooked food which is served hot, and carbonated,
commercially bottled beverages are usually safe.

Prudent dietary and hygienic practices will prevent most, but not all, cases of TD.
Antimicrobial agents are discouraged for prevention except in special circumstances
and in high-risk hosts as widespread usage in millions of travelers would be associated
with a significant number of side effects (including some severe ones) while preventing
a disease that has had no reported mortality. Instead of universal antimicrobial
prophylaxis, a more sensible approach is rapid institution of effective treatment that
can shorten the disease to 30 hours or less in most people. For mild diarrhea, an
antimotility drug such as diphenoxylate or loperamide can be taken. Alternatively,
bismuth subsalicylate, which works somewhat slower, can be used. For more severe
diarrhea, an antimicrobial drug may be used for treatment - trimethoprim-sulfamethoxazole,
trimethoprim alone, ciproflaxin, and doxycycline are among the choices. These drugs
should be carried by the traveler for use in the event of illness. Oral rehydration
needs to be instituted when necessary. The presence of fever, bloody stool, abdominal
pain, or profound dehydration indicates a more severe infection requiring medical attention.

What does the literature say?

DuPont HL, et al (Rev Infect Dis 1990 Jan-Feb;12 Suppl 1:S64-7; Use of bismuth
subsalicylate for the prevention of travelers' diarrhea) in
July 1977 and July 1985 enrolled students from the United States participated in a
double-blind, placebo-controlled trial examining the effectiveness of liquid bismuth
subsalicylate (BSS) (1977) and two dosages of the tablet formulation of BSS (1985) in
preventing diarrhea while visiting Guadalajara, Mexico. In the first study, 62 subjects
received BSS for 3 weeks at a dosage of 60 mL four times daily (4.2 g of BSS/d) compared
with 66 students receiving an oral placebo on a similar dosing schedule. In the second
study, 51 students took two tablets four times daily (2.1 g of BSS/d), 63 took one tablet
four times daily (1.05 g of BSS/d), and 58 took a placebo (two tablets taken four times
daily), each for 3 weeks. In the initial study, 23% BSS-treated subjects developed
diarrhea compared with 61% placebo-tested persons. In the second trial, 14% of the
subjects taking two tablets of BSS four times daily, 24% taking one tablet of BSS four
times daily, and 40% receiving placebo experienced diarrhea (P less than .001 for
the higher dose). In cases in which stools were analyzed, 24% of the BSS-treated
subjects who had diarrhea had a detectable enteric pathogen, compared with 59% of
those randomized to receive a placebo. BSS was well tolerated and it was speculated
that either bismuth or the intestinal hydrolysis products of BSS have direct
antimicrobial effects.

Ericsson CD et al (Antimicrob Agents Chemother 1992 Dec;36(12):2821-4; Optimal dosing of
trimethoprim-sulfamethoxazole when used with loperamide to treat traveler's diarrhea.)
explored the optimal dosing regimen for trimethoprim-sulfamethoxazole (TMP-SMX) used in
combination with loperamide to treat traveler's diarrhea. They looked at 190 U.S.
adults with acute diarrhea enrolled in a double-blind, randomized trial in Guadalajara,
Mexico. All patients received Immodium (loperamide 4-mg loading dose; 2 mg after each
loose stool, not to exceed 16 mg/day for 3 days) and were randomized to receive a
3-day course of TMP-SMX (160:800 mg twice daily for six doses) (group A), a single large
dose of TMP-SMX (320:1,600 mg) (group B), or a large loading dose (320:1,600 mg) followed
by standard doses for 3 days (160:800 mg twice daily for five doses) (group C).
Patients in group C responded best (P < 0.01), with 75% of subjects recovered from
diarrhea in 12 h compared with 34 h (group A) and 33 h (group B). Similar differences
in favor of group C were noted in the subset of patients who presented with moderate to
severe diarrhea. On average, patients in group C took significantly (P < 0.05) less
loperamide (1.2 mg) after the 4-mg loading dose compared with patients in group A (2.4 mg)
or group B (2.0 mg). They concluded that the most efficacious treatment of traveler's
diarrhea in the interior of Mexico is to take loperamide in usual doses to control symptoms
in combination with a single large dose of TMP-SMX, which should then be continued for 3
days in standard doses.

And what about the ciproflaxin type antibiotics? DuPont HL et al (Antimicrob Agents
Chemother 1992 Jan;36(1):87-91; Five versus three days of ofloxacin therapy for traveler's
diarrhea: a placebo-controlled study. ) studied 232 students visiting Mexico, comparing
300 mg of ofloxacin given orally twice daily for either 3 or 5 days with placebo for the
treatment of acute diarrhea. They found a 3-day regimen of ofloxacin to be as effective
as the 5-day regimen in producing a clinical and microbiologic cure. Clinical cures
for patients who received ofloxacin for 5 days occurred in 89% of subjects, whereas
clinical cure occurred in 95% of those who received ofloxacin for 3 days and in 71% of
those who took placebo. There was no significant difference in the number of adverse
events reported by patients in either of the treatment groups.

Does adding an anti diarrheal agent have any negative effects? Ericsson CD et al
(J Travel Med 1997 Mar 1;4(1):3-7; Single Dose Ofloxacin plus Loperamide Compared with
Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea.) studied
the antimicrobial oroflaxin (similar to ciproflaxin). This prospective, randomized,
evaluator-blinded treatment trial was again conducted in Guadalajara, Mexico, during the
summers of 1992-1994. Adults newly arrived in Mexico from the United States who developed
acute diarrhea of less than 2 weeks' duration were randomized to receive orally either:
A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or
C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose
stool, not to exceed 16 mg per day, for 3 days. Ofloxacin and loperamide were well
tolerated. Combination therapy with single dose ofloxacin plus loperamide was
significantly more efficacious in reducing the duration of diarrhea than single dose
ofloxacin or ofloxacin given for 3 days without the antimotility agent(p
Sixty-three percent of subjects passed no further unformed stools after the initial
doses of combination therapy, and 91% were well by the end of the first 24 hours.
Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe
and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone.

And there is good evidence that even a single dose of antimicrobial agents may be enough.
Petruccelli BP et al (J Infect Dis 1992 Mar;165(3):557-60; Treatment of traveler's
diarrhea with ciprofloxacin and loperamide) studied the efficacy of loperamide given
with long- and short-course quinolone therapy for treating traveler's diarrhea. 142 US
military personnel were randomized to receive a single 750-mg dose of ciprofloxacin with
placebo, 750 mg of ciprofloxacin with loperamide, or a 3-day course of 500 mg of
ciprofloxacin twice daily with loperamide. Of the participants, 87% completely recovered
within 72 h of entry. Total duration of illness did not differ significantly among the
three treatment groups, but patients in the 3-day ciprofloxacin plus loperamide group
reported a lower cumulative number of liquid bowel movements at 48 (1.8 vs 3.6) and 72 h
(2.0 vs 3.9) after enrollment compared with patients in the single-dose ciprofloxacin
plus placebo group.

The bottom line:

generally self limited, traveler's diarrhea (TD) is more of an inconvenience than a
life-threatening process

prevention is the mainstay of therapy in this illness, and education to understand and
avoid risk factors is the first step

antimicrobial agents are not recommended for prevention in most cases

in high risk areas, it may be useful to use pepto bismol tablets, 2 - 4x a day for prevention

for mild diarrhea, an antimotility drug such as diphenoxylate or loperamide can be taken

more severe diarrhea, an antibiotic may be used for treatment - and a short
course of 1 to 3 days (with an antimotility agent) should be more than adequate